Full contour breast implant

ABSTRACT

Full contour absorbable implants for breast surgery redistribute breast volume between the breast&#39;s upper and lower poles in exact and desirable ratios. The implants preferably redistribute breast volume so that the upper pole breast volume is 20-40% of the total volume, and the lower pole breast volume is 60-80% of the total volume. The implants are also designed to provide specific curvatures to the poles of the breast, and to angulate the nipple areolar complex slightly skyward so that the patient&#39;s nipple is positioned at an angle above the nipple meridian reference line. The implants are designed to be transitory, with sufficient strength retention to allow transition from support of the breast by the implant to support by regenerated host tissue growing in and around the implants, without any significant loss of support during or subsequent to remodeling. The implants may optionally be used with permanent breast implants.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/628,739, filed Feb. 9, 2018, entitled “FULL CONTOUR BREAST IMPLANT”,the entire contents of which are incorporated herein by reference intheir entirety for all purposes.

FIELD OF THE INVENTION

The present invention generally relates to absorbable implants that canbe used to shape the volumetric distribution of the breast soft tissuein the upper and lower poles of the breast, the projection of thebreast, the curvatures of the upper and lower poles of the breast, andthe position and angulation of the nipple, and are designed for use inplastic surgery procedure.

BACKGROUND OF THE INVENTION

Numerous plastic surgery procedures are performed each year to restoreor correct the form or function of the body. Many of these proceduresseek to restore a youthful appearance, or even to enhance one's existingappearance. Natural factors, such as aging and gravity, contribute tothe loss of the youthful appearance. For example, skin laxity, loss ofmuscle tone, and attenuation of ligaments can result in ptosis(drooping) of the breast. Plastic surgeons have developed a plethora ofsurgical techniques to correct the ptosis of different anatomicalstructures that occurs with aging. These techniques vary in the type ofincision, direction of incision, plane of dissection, amount ofdissection, extent of repositioning of tissue, the use of differenttypes of sutures, different suturing techniques, and different fixationtechniques. Almost all of them rely on the use of the pre-existing skinenvelope as the support system for the newly lifted tissue. Theseapproaches almost invariably result in recurrent ptosis, since thesurgeon is merely relying on the aging and sagging surrounding tissuesthat have already failed to provide the necessary support to maintain anormal appearance. For example, de-epithelialization, flaptransposition, gland repositioning or suturing will not alter thephysical properties of the patient's tissue. At most, these techniquesonly slow recurrent ptosis by creating internal scars that providelimited reinforcement. And even the scarring process varies from patientto patient making this limited approach highly unpredictable. Notably,there is no attempt with these approaches to change the physicalproperties of the local tissue in order to improve the outcome.

Several surgeons have attempted to reinforce their lift procedures usingsurgical meshes in mastopexy and breast reconstruction procedures. Someof these techniques have also incorporated the use of variousreinforcing materials similar to those used in hernia repair, such asflat polymeric meshes, allografts, xenografts and autografts.

In 1981, Johnson described the use of MARLEX® (crystallinepolypropylene) mesh to convert the support of breast tissue aftermastopexy from a cutaneous origin to a skeletal origin by attaching themesh to the area of the second rib, (Johnson, Aesth. Plast. Surg.5:77-84 (1981)). The flat MARLEX® mesh is a permanent mesh made frompolypropylene, and was implanted to provide two slings in each breastthat supported the breast tissue. It is not replaced with regeneratedhost tissue.

Auclair and Mitz have described a mesh assisted mastopexy using a flatabsorbable mesh and a periareolar skin resection technique (Auclair andMitz, Ann. Chir. Plast. Esthdt. 38:107-113 (1993)). A rapidly absorbingVICRYL® mesh was placed around the anterior surface of the breast glandin order to form an internal bra.

Goes has reported the use of polyglactin 910 (an absorbable copolymer of90% glycolide and 10% L-lactide, also known as VICRYL®) and a mixed mesh(containing 60% polyglactine 910 and 40% permanent polyester) in aperiareolar mammoplasty using a double skin technique (Góes, Plast.Reconstr. Surg. 97:959-968 (1996)). The technique involves dissectingthe soft tissue envelope away from the parenchyma, and wrapping thebreast parenchyma with a mesh to help provoke the formation of avigorous connective scar to produce a breast lining structure that wouldbe less susceptible to ptosis. The soft tissue envelope is then closedaround the parenchyma. In the procedure, a dermal flap was createdaround the nipple-areolar complex, and after the lift procedure wascompleted, the dermal flap was sutured on top of the breast gland toprovide an internal cutaneous lining. The mesh was then sutured on topof the dermal flap so that it surrounded the breast gland, and the endsof the mesh were sutured together in the central part of the superioraspect of the breast to form a conical breast shape with slightelevation of the breast. Although the mesh was found to provideshort-term support, it was absorbed after 3 months, and better resultswere reported with the mixed (partially absorbable) mesh. The latterprovided a less elastic envelope, avoided tissue displacement, andimproved the quality and duration of the new breast shape (Sampaio Goes,Clin. Plast. Surg. 29:349-64 (2002)).

U.S. Pat. No. 6,210,439 to Firmin et al. discloses a circular VICRYL®mesh with a V-shaped opening extending from its center that has ametallic reinforcing wire running around the periphery. The implantassumes a conical shape suitable for mammoplasty when the reinforcingwire is tightened.

However, VICRYL® mesh degrades rapidly in vivo with 50% loss of strengthretention at five days, no residual strength at 10-14 days, and completeabsorption at 42 days. This strength retention profile provides verylittle time for the formation of regenerated host tissue that canwithstand the forces exerted on the breast. In fact, Góes and Batesconcluded “absorbable synthetic meshes do not persist sufficiently tohave an impact on the recurrence of breast ptosis” [see Goes and Bates,Periareolar mastopexy with FortaPerm, Aesth. Plast. Surg 34:350-358(2010)].

U.S. Pat. No. 7,476,249 to Frank discloses an implantable sling shapedprosthesis device for supporting and positioning a breast implant in apatient, wherein the device is configured from a sheet of a chemicallyinert permanent material, such as polytetrafluoroethylene or silicone,to support the breast implant. The sling shaped device provides supportto the breast but does not have shape memory that allows it to confershape to the breast or retain a three-dimensional shape.

US Patent Application Publication No. 2009/0082864 by Chen et al. alsodiscloses a prosthetic device for supporting a breast implant made froma mesh. The device has a flat back wall, a concave front wall, and acurved transitional region between these walls that forms a smoothlycurved bottom periphery.

U.S. Pat. No. 7,670,372 to Shfaram et al. discloses a minimally invasivebreast lifting system. The system incorporates a biological material,such as tendons, or synthetic material, such as silicone or GOR-TEX®material (polytetrafluoroethylene), to cradle the breast.

US Patent Application Publication No. 2012/0283826 by Moses et al.discloses mastopexy systems having an insertion device, a suspensionstrut, and a lower pole support. The implanted suspension strut providespole projection and attachment points for the lower pole support, andthe lower pole support can lift the lower pole of the breast.

US Patent Application Publication No. 2008/0097601 by Codori-Hurff etal. discloses mastopexy and breast reconstruction procedures assisted bythe use of processed tissue material derived from intestine or dermis.The tissue material is cut to a crescent shape, and may have up to 10layers bonded together. The bonded layers can be chemicallycross-linked.

US Patent Application Publication No. 2008/0027273 by Guttermandiscloses a minimally invasive mastopexy system having a soft tissuesupport sling. The latter can be made from polyethylene, PEBAX®(polyether block amide), PEEK (polyether ether ketone), nylon, PET(polyethylene terephthalate), ePTFE (polytetrafluoroetylene), silicone,or even a metal lattice. The device is designed to provide support bysuspending the breast from the upper pole region using a bone anchor.

US Patent Application Publication No. 2010/0331612 by Lashinski et al.discloses a system for performing a minimally invasive mastopexy (breastlift) that can include an elongate flexible sling used as a soft tissueanchor. The sling can be made from a mesh, and the mesh can be made, forexample, from polypropylene. The sling is designed to resist weakeningor degradation when implanted.

US Patent Application No. 20100217388 to Cohen discloses cradlingmembers for soft tissue shaping of the breast.

US Patent Application No. 20160038269 to Altman discloses variousimplants for supporting the breast after surgery. The implants are madefrom silk.

US Patent Application Publication No. 20120185041 to Mortarino et al.discloses methods for using silk meshes in breast augmentation andbreast reconstruction with a knit pattern that substantially preventsunraveling when cut. Mortarino does not disclose silk meshes withthree-dimensional shapes that confer shape to the breast.

US Patent Application No. 20130304098 to Mortarino discloses implants inthe form of pockets that can be used in breast reconstruction. Theimplants are made from silk.

Notably, there is very little innovation in the design of implants thatwhen implanted can simplify breast surgery, provide specific shapes tothe upper and lower poles of the breast, and angulate the nipple at adesirable projection above the nipple meridian reference (NMR) line.

Mallucci and Branford, Concepts in aesthetic breast dimensions: Analysisof the ideal breast, JPRAS, 65:8-16 (2010) analyzed the vertical heightsin the coronal plane of the upper and lower poles of the breasts of 100models, and concluded that the ideal ratio of the vertical height of theupper pole of the breast to the vertical height of the lower pole of thebreast in the coronal plane should be 45:55. Any significant deviationfrom this ratio was considered to result in a less attractive breastshape. The authors subsequently used these findings to develop animproved method for breast augmentation using permanent breast implants(see Mallucci and Branford, Design for natural breast augmentation: TheICE principle, Plast. Reconstr. Surg. 137:1728-1737 (2016)). However,amongst other things, the investigators did not describe or showimplants to redistribute volume, depth, or slope in the breast tosimplify the augmentation procedure and achieve consistent results.

WO 2009/001293 to Lauryssen discloses a permanent implant (made frompolypropylene or polyester) in the shape of a cup, more specifically asemi-ovoid shape, that can be used in mesh assisted mastopexy. Thedescribed cup has a lower end that is larger than its upper end. Thedescribed implant also has a convex lower pole curve and a convex upperpole curve as shown in FIG. 3 of WO 2009/001293 to Lauryssen. Theimplant is not designed to angulate the patient's nipple. Rather theimplant has an aperture for the nipple areola complex that is locatedmore inferior than superior (as shown in FIG. 3 of WO 2009/001293).

WO 2006/117622 by Lauryssen et al. also discloses a permanent implantfor soft tissue support of the breast that is generally L-shaped orU-shaped, but is made from polypropylene.

A permanent implant for soft tissue support, made frompolytetrafluoroethylene (ePTFE), which can be used in forming apredetermined breast shape has been disclosed by WO 2004/096098 byHamilton el al. The implants do not degrade in vivo, and are notdesigned to angulate the patient's nipple above the nipple meridianreference (NMR) line.

Van Deventer et al. has reported the use of an internal breast supportsystem for mastopexy using a partially degradable mesh that was formedinto a cone by overlapping the ends of the mesh (van Deventer et al.Aesth. Plast. Surg. 36:578-89 (2012)). The mesh contained 50%polypropylene and 50% absorbable polyglactin.

U.S. Pat. No. 9,532,867 to Felix discloses absorbable implants forbreast surgery that support newly lifted breast parenchyma. The shapesof the implants include generally symmetrical shapes such as domes, andhemispheres.

Despite the advances described above, surgeons still lack an implantthat can produce a defined aesthetically pleasing outcome in breastsurgery without extensive manipulation of tissues and use of implants,including sutures, meshes and permanent breast implants.

SUMMARY OF THE INVENTION

Implants described herein assist the surgeon in reshaping the breastwith a predefined aesthetically pleasing shape.

In embodiments, an implant is engineered with a desired shape thatproduces specific volumetric ratios of soft tissue in the upper andlower poles of the breast.

In embodiments, the implant produces a specific angulation of thenipple, specific curvatures of the upper and lower poles, and controlsthe extent of protrusion of the breast from the chest wall. The surgeonis able to show the implant options to the patient prior to surgery sothe patient can select a specific size, and better appreciate theexpected outcome of surgery.

In embodiments, in addition to providing a specific breast shape, theimplant is absorbable, permits tissue in-growth, degrades in acontrolled manner, and is replaced over time with the patient's owntissue. The implant preferably comprises a polymeric material with apredictable rate of degradation, and a predictable strength retention invivo.

In embodiments, the implant retains strength long enough to allow thesupport of the breast to be transitioned from the implant to new tissuewithout any loss of support for the breast tissue.

In embodiments, the implant has a pre-determined three-dimensional shapethat can be implanted subcutaneously to cover the entire breast, betweenthe skin and the breast mound of the breast, excluding the nippleareolar complex (NAC). The implant allows the surgeon to easily controlthe volumetric ratios of the upper and lower poles of the breast, theextent of protrusion of the breast from the chest wall, and thecurvatures of the upper and lower poles of the breast.

In embodiments, the implant has a full contour design and provides ameans for the surgeon to produce a breast with a highly desirableappearance allowing the shapes and volumes of the upper and lower breastto be re-modeled in a single procedure. In addition, the implant allowsthe surgeon to position and angle the nipple on the breast at a verydesirable, slightly skyward, location.

In embodiments, the implant serves to provide the surgeon with a meansto deliver cells, stem cells, gels, hydrogels, bioactive agents, fattytissue, autologous fat, fat lipoaspirate, injectable fat, adipose cells,fibroblast cells, and other materials to the implant site.

In embodiments, the breast implant is used with a permanent breastimplant, such as a silicone or saline breast implant. The implant couldalso comprise bioactive agents. In other embodiments, the implant isdesigned to produce a specific breast shape and angulation of thenipple. These implants are configured/designed to produce a breast shapewith a specific volumetric ratio of the upper pole volume to the lowerpole volume.

In embodiments, implants are configured/designed to produce a specificbreast shape where the nipple is angulated at an angle that is 12-27degrees above the nipple meridian reference (NMR) line, more preferably18-22 degrees above the NMR.

In embodiments, the implants are porous and absorbable, with an openingfor the nipple areola structure, function as transitory scaffolds thatcontour the breast and provide initial support to the breast, butdegrade over time, and are replaced with host tissue. The implants canbe used without or with permanent breast implants. The implants arepreferably sutured in place, and have suture pullout strengths that aresufficient to resist the mechanical loads exerted on the implant. Theimplants can be made from poly-4-hydroxybutyrate (P4HB) and copolymersthereof. In embodiments, implants can be made from P4HB and copolymersthereof in the form of a mesh, and preferably a monofilament mesh.

In one embodiment, the implants have a three-dimensional shape that: (i)can redistribute or organize the tissue volume in the breast such thatthe upper pole volume (UPV) of the breast is between 20-40%, and morepreferably 25-35%, and the lower pole volume (LPV) of the breast isbetween 60-80%, and more preferably 65-75%, and more preferably wherethe ratio of the UPV to LPV ranges from 20:80 to 40:60, and morepreferably from 25:75 to 35:65, and in one embodiment is 28:72, and (ii)angulates the patient's nipple 12 (or 13) to 27 degrees above the nipplemeridian reference (NMR) line, more preferably 18-22 degrees above theNMR line. The implants comprise an opening for the nipple areolastructure. The implants are preferably absorbable and porous, andreplaced in vivo by host tissue.

In embodiments, an implant is configured to redistribute the tissuevolume in the breast such that the upper pole volume (UPV) of the breastis between 20-40% and the lower pole volume (LPV) of the breast isbetween 60-80%, and wherein the implant angulates the patient's nipple12 (or 13) to 27 degrees above the nipple meridian reference (NMR) line,more preferably 18-22 degrees above the NMR line. The use of apre-shaped implant for the entire breast that can contour andredistribute tissue volume and angulate the patient's nipple withdefined precision would be particularly desirable, and even moredesirable if the scaffold is transitory and is replaced over time withhost tissue.

In embodiments, an implant is configured to produce a remodeled breastwith a UPV of 25-35%, and a LPV of 65-75%, more preferably wherein theratio of the UPV to the LPV in the breast is 28:72.

In embodiments, an implant is configured to provide a surgeon with animplant for breast surgery that can precisely angulate the patient'snipple, preferably wherein the implant angulates the patient's nipple 12(or 13) to 27 degrees above the nipple meridian reference (NMR) line,more preferably 18-22 degrees above the NMR line.

In embodiments, an implant is configured to provide a surgeon with animplant for breast surgery that can be used to produce a remodeledbreast with a UPV of 25-35%, and a LPV of 65-75%, more preferablywherein the ratio of the UPV to the LPV in the breast is 28:72, andwherein the implant angulates the patient's nipple 12 (or 13) to 27degrees above the nipple meridian reference (NMR) line, more preferably18-22 degrees above the NMR line, and wherein the implant is atransitory scaffold that degrades and allows a transition from supportof the breast by the scaffold to support by regenerated host tissue.

In an embodiment, an implant is configured with an upper pole, a lowerpole, and wherein the ratio of the volume of the upper pole to the lowerpole is less than 1.

In an embodiment, an implant is configured with an upper pole, a lowerpole, and an aperture for the nipple areola complex (NAC), wherein theratio of the volume of the upper pole to the lower pole is less than 1,and wherein the aperture is positioned on the implant to angulate theNAC, after implantation, so that the angle between the nipple projectionline and the nipple meridian reference line is greater than 1 degree.

In embodiments, a superior end of the implant has a size equal to orgreater than the inferior end of the implant.

In embodiments, the implant comprises an annular shaped flexible pillarcircumferentially disposed about the NAC aperture.

In embodiments, the implant further comprises a plurality of reinforcingpillars or ribs radially extending from the NAC aperture feature to theouter edge of the implant.

In embodiments, the implant comprises a plurality of tissue-attachmenttabs radially extending from a rearward edge the implant. Inembodiments, the tabs extend from 3,6,9 and 12 o'clock positions.

In embodiments, an implant is configured to provide implants for breastsurgery that can be used with or without implants, and that can betemporarily deformed for implantation.

In embodiments, an implant is configured to provide methods to produceimplants that can be used to remodel a breast so that the breast has aUPV of 25-35%, and a LPV of 65-75%, more preferably wherein the ratio ofthe UPV to the LPV in the breast is 28:72, and wherein the implantangulates the patient's nipple 12 (or 13) to 27 degrees above the nipplemeridian reference (NMR) line, more preferably 18-22 degrees above theNMR line.

In embodiments, an implant is configured to provide methods to implantthe implants, and produce a breast with a UPV of 25-35%, and a LPV of65-75%, more preferably wherein the ratio of the UPV to the LPV in thebreast is 28:72, and wherein the implant angulates the patient's nipple12 (or 13)-27 degrees above the nipple meridian reference (NMR) line,more preferably 18-22 degrees above the NMR line.

In embodiments, a kit for assisting the physician to reshape the breastcomprises a plurality of sterile guides each of which defines a breastshape having an UPV of 25-35% of the total breast volume, and an openingto angulate the patient's nipple between 10-30 degrees.

In embodiments, a method of reshaping the breast of a patient comprisesdetermining at least one target percent that the upper pole of thebreast shall occupy relative to the total target volume of the breast;selecting an implant from a kit of candidate implants shaped to hold themound of the breast such that the upper pole of the breast occupies thetarget percent of the total breast volume after implantation; andimplanting the selected implant into the breast between the breast moundand the skin.

In embodiments, the each of the candidate implants of the kit has atarget percent between 25 and 35%.

In embodiments, each of the candidate implants of the kit has a NACaperture that angulates the nipple between 10-30 degrees skyward.

In embodiments, the lower pole of each of the candidate implants of thekit has a convex curvature.

In embodiments, the upper pole of each of the candidate implants of thekit has a concave curvature, or in other embodiments, is noncurved orstraight.

These advantages as well as other objects and advantages of the presentinvention will become apparent from the detailed description to follow,together with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1-5 are side views of a breast shown in various shapes;

FIGS. 6A-6D show various views of an implant for supporting a breast inaccordance with an embodiment of the invention;

FIG. 7A is a diagram showing an isometric view of a full contour implantin accordance with an embodiment of the invention;

FIGS. 7B-7C are diagrams showing upper and lower pole volumesrespectively of the implant shown in FIG. 7A;

FIGS. 7D-7E are diagrams showing isometric and left profile viewsrespectively of the implant after implantation in a breast;

FIG. 8A is a diagram showing an isometric view of an example of athree-dimensional mold that can be used to manufacture a full contourbreast implant;

FIG. 8B is a diagram showing a cross-sectional view of a mesh positionedin the mold shown in FIG. 8A for thermoforming into a full contourbreast implant in accordance with an embodiment of the invention;

FIG. 9 depicts a mesh implant fastened in a mold with excess meshvisible around the outside edge of the mold;

FIG. 10 depicts a full contour implant made in accordance with anembodiment of the invention;

FIG. 11 depicts another full contour implant including an opening toreceive the patient's NAC;

FIG. 12 depicts another full contour implant including a plurality tabsextending from its outer edge;

FIG. 13 depicts another full contour implant held in a mold; and

FIGS. 14-15 are diagrams showing left side and front views respectivelyof another implant including an ancillary layer.

DETAILED DESCRIPTION OF THE INVENTION

Before the present invention is described in detail, it is to beunderstood that this invention is not limited to particular variationsset forth herein as various changes or modifications may be made to theinvention described and equivalents may be substituted without departingfrom the spirit and scope of the invention. As will be apparent to thoseof skill in the art upon reading this disclosure, each of the individualembodiments described and illustrated herein has discrete components andfeatures which may be readily separated from or combined with thefeatures of any of the other several embodiments without departing fromthe scope or spirit of the present invention. In addition, manymodifications may be made to adapt a particular situation, material,composition of matter, process, process act(s) or step(s) to theobjective(s), spirit or scope of the present invention. All suchmodifications are intended to be within the scope of the claims madeherein.

Methods recited herein may be carried out in any order of the recitedevents which is logically possible, as well as the recited order ofevents. Furthermore, where a range of values is provided, it isunderstood that every intervening value, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range is encompassed within the invention. Also, it iscontemplated that any optional feature of the inventive variationsdescribed may be set forth and claimed independently, or in combinationwith any one or more of the features described herein.

All existing subject matter mentioned herein (e.g., publications,patents, patent applications and hardware) is incorporated by referenceherein in its entirety except insofar as the subject matter may conflictwith that of the present invention (in which case what is present hereinshall prevail).

Reference to a singular item, includes the possibility that there areplural of the same items present. More specifically, as used herein andin the appended claims, the singular forms “a,” “an,” “said” and “the”include plural referents unless the context clearly dictates otherwise.It is further noted that the claims may be drafted to exclude anyoptional element. As such, this statement is intended to serve asantecedent basis for use of such exclusive terminology as “solely,”“only” and the like in connection with the recitation of claim elements,or use of a “negative” limitation.

Now turning to FIGS. 1-2, various patient anatomy and anatomicallandmarks are depicted for facilitating understanding of the invention.Particularly, FIG. 1 is a diagram showing a cross-section of a breast 10in an aesthetically pleasing breast shape. The volume or area occupiedby the upper pole is shown as the area with the diagonal parallel linesand reference numeral 20. The volume or area occupied by the lower poleis shown as the shaded area and reference numeral 30. The diagram alsoshows the chest wall reference (CWR) line 12, and positions of the upperpole reference (UPR) 22, upper pole curve (UPC) 24, lower pole reference(LPR) line 32, lower pole curve (LPC) 34, NAC (nipple areolar complex)plane 40, and the angulation of the NAC measured from the nipplemeridian reference (NMR) line 50 to the nipple projection line (NPL) 52.

FIG. 2 is another diagram showing a three-quarter profile of the breast,the upper pole volume (UPV) 20 and lower pole volume (LPV) 30 of thebreast, the NAC angulation of the nipple on the breast pointing slightlyskyward, and a ratio of the height of the upper pole of the breast tothe lower pole of the breast equal to 70:40 when measured along thenatural sloping chest wall reference (CWR) line 12.

To further assist in understanding the following definitions are setforth below. However, it is also to be appreciated that unless definedotherwise as described herein, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this invention belongs.

Definitions

“Absorbable” as generally used herein means the material is degraded inthe body, and the degradation products are eliminated or excreted fromthe body. The terms “absorbable”, “resorbable”, “degradable”, and“erodible”, with or without the prefix “bio”, can be usedinterchangeably herein, to describe materials broken down and graduallyabsorbed, excreted, or eliminated by the body, whether degradation isdue mainly to hydrolysis or mediated by metabolic processes.

“Bioactive agent” as generally used herein refers to therapeutic,prophylactic or diagnostic agents, preferably agents that promotehealing and the regeneration of host tissue, and also therapeutic agentsthat prevent, inhibit or eliminate infection. “Bioactive agent” includesa single such agent and is also intended to include a plurality.

“Blend” as generally used herein means a physical combination ofdifferent polymers, as opposed to a copolymer formed of two or moredifferent monomers.

“Burst strength” as generally used herein is determined according toASTM D6797-02 (Standard Test Method for Bursting Strength of FabricsConstant-Rate-of-Extension (CRE) Ball Burst Test) at ambient conditionsusing a ball burst fixture with a 1.6 cm circular opening and a 1 cmdiameter half-rounded probe.

“Copolymers of poly-4-hydroxybutyrate” as generally used herein meansany polymer containing 4-hydroxybutyrate with one or more differenthydroxy acid units.

“Endotoxin content” as generally used herein refers to the amount ofendotoxin present in an implant or sample, and is determined by thelimulus amebocyte lysate (LAL) assay.

“Inframammary fold” or “IMF” as generally used herein is the positionwhere the lower pole of the breast meets the chest wall.

“Lower pole” as generally used herein means the part of the breastlocated between the inframammary fold (IMF) and the nipple meridianreference, and protruding away from the chest wall.

“Lower pole reference” or “LPR” as generally used herein is a line thatextends perpendicular from the chest wall, starting just below theinframammary fold, and just touches the lowest projection of the lowerpole of the breast as shown in FIG. 1.

“Lower pole volume” or “LPV” as generally used herein means the volumeof tissue in the lower pole of the breast as shown in FIG. 2. The volumeof tissue is contained within the boundaries defined by the lower polecurve, the chest wall and the nipple projection line (NPL).

“Molecular weight” as generally used herein, unless otherwise specified,refers to the weight average molecular weight (Mw), not the numberaverage molecular weight (Mn), and is measured by GPC relative topolystyrene.

“NAC angulation” or nipple angle as generally used herein means theangle between the nipple meridian reference (NMR) line and the nippleprojection line” or “NPL” as shown in FIG. 1.

“Nipple meridian reference” or “NMR” is the plane drawn horizontallythrough the nipple to the chest wall as shown in FIG. 1.

“Nipple projection line” or “NPL” as generally used herein means theline drawn perpendicular to the chest wall through the nipple as shownin FIG. 1.

“Poly-4-hydroxybutyrate” as generally used herein means a homopolymercontaining 4-hydroxybutyrate units. It can be referred to herein as P4HBor TephaFLEX® biomaterial (manufactured by Tepha, Inc., Lexington,Mass.).

“Suture pullout strength” as generally used herein means the peak load(kg) at which an implant fails to retain a suture. It is determinedusing a tensile testing machine by securing an implant in a horizontalholding plate, threading a suture in a loop through the implant at adistance of 1 cm from the edge of the implant, and securing the suturearms in a fiber grip positioned above the implant. Testing is performedat a crosshead rate of 100 mm/min, and the peak load (kg) is recorded.The suture is selected so that the implant will fail before the suturefails.

“Upper pole” as generally used herein means the top part of the breastlocated between the upper pole reference and the nipple meridianreference, and protruding away from the chest wall.

“Upper pole reference” or “UPR” as generally used herein is the positionat the top of the breast where the breast takes off from the chest wall,and is shown in FIG. 1.

“Upper pole volume” or “UPV” as generally used herein means the volumeof tissue in the upper pole of the breast as shown in FIG. 2. The volumeof tissue is contained within the boundaries defined by the upper polecurve, the chest wall and the nipple projection line (NPL).

Materials for Preparing Full Contour Breast Implants

In embodiments, implants that can be used to remodel the shape of thebreast, the upper and lower pole volumes, the protrusion of the breastfrom the chest wall, and the angulation of the nipple on the breast havebeen developed using a wide variety of materials. The implants producesafe biocompatible and an aesthetically pleasing breast byredistributing and organizing tissue volume in the breast so that thereis a specific volumetric ratio of tissue in the upper breast relative tothe lower breast, specific curvatures of the upper pole and lower pole,and specific angulation of the nipple on the breast. Optionally, theimplants may be used with permanent breast implants such as silicone andsaline breast implants as well as other bulking materials and tissues.

A. Polymers for Preparing Full Contour Breast Implants

The full contour breast implants may comprise permanent materials, suchas non-degradable thermoplastic polymers, including polymers andcopolymers of ethylene and propylene, including ultra-high molecularweight polyethylene, ultra-high molecular weight polypropylene, nylon,polyesters such as poly(ethylene terephthalate),poly(tetrafluoroethylene), polyurethanes, poly(ether-urethanes),poly(methylmethacrylate), polyether ether ketone, polyolefins, andpoly(ethylene oxide). However, the implants preferably comprisedegradable materials, more preferably thermoplastic or polymericdegradable materials, and even more preferably the implants are madecompletely from degradable materials.

In a preferred embodiment, the implants are made from one or moreabsorbable polymers, preferably absorbable thermoplastic polymers andcopolymers. The implant may, for example, be prepared from polymersincluding, but not limited to, polymers of glycolic acid, lactic acid,1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid,4-hydroxybutyrate, ε-caprolactone, including polyglycolic acid,polylactic acid, polydioxanone, polycaprolactone, copolymers of glycolicand lactic acids, such as VICRYL® polymer, MAXON® and MONOCRYL®polymers, and including poly(lactide-co-caprolactones);poly(orthoesters); polyanhydrides; poly(phosphazenes);polyhydroxyalkanoates; synthetically or biologically preparedpolyesters; polycarbonates; tyrosine polycarbonates; polyamides(including synthetic and natural polyamides, polypeptides, andpoly(amino acids)); polyesteramides; poly(alkylene alkylates);polyethers (such as polyethylene glycol, PEG, and polyethylene oxide,PEO); polyvinyl pyrrolidones or PVP; polyurethanes; polyetheresters;polyacetals; polycyanoacrylates; poly(oxyethylene)/poly(oxypropylene)copolymers; polyacetals, polyketals; polyphosphates;(phosphorous-containing) polymers; polyphosphoesters; polyalkyleneoxalates; polyalkylene succinates; poly(maleic acids); silk (includingrecombinant silks and silk derivatives and analogs); chitin; chitosan;modified chitosan; biocompatible polysaccharides; hydrophilic or watersoluble polymers, such as polyethylene glycol, (PEG) or polyvinylpyrrolidone (PVP), with blocks of other biocompatible or biodegradablepolymers, for example, poly(lactide), poly(lactide-co-glycolide, orpolycaprolactone and copolymers thereof, including random copolymers andblock copolymers thereof. Preferably the absorbable polymer or copolymerwill be substantially resorbed after implantation within a 1 to 24-monthtimeframe, more preferably 3 to 18-month timeframe, and retain someresidual strength for at least 2 weeks to 3 months.

Blends of polymers, preferably absorbable polymers, can also be used toprepare the full contour breast implants. Particularly preferred blendsof absorbable polymers are prepared from absorbable polymers including,but not limited to, polymers of glycolic acid, lactic acid,1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyric acid,4-hydroxybutyrate, ε-caprolactone or copolymers thereof.

In a particularly preferred embodiment, poly-4-hydroxybutyrate (Tepha'sP4HB™ polymer, Lexington, Mass.) or a copolymer thereof is used to makethe implant. Copolymers include P4HB with another hydroxyacid, such as3-hydroxybutyrate, and P4HB with glycolic acid or lactic acid monomer.Poly-4-hydroxybutyrate is a strong, pliable thermoplastic polyester thatis biocompatible and resorbable (Williams, et al. Poly-4-hydroxybutyrate(P4HB): a new generation of resorbable medical devices for tissue repairand regeneration, Biomed. Tech. 58(5):439-452 (2013)). Uponimplantation, P4HB hydrolyzes to its monomer, and the monomer ismetabolized via the Krebs cycle to carbon dioxide and water. In apreferred embodiment, the P4HB homopolymer and copolymers thereof have aweight average molecular weight, Mw, within the range of 50 kDa to 1,200kDa (by GPC relative to polystyrene) and more preferably from 100 kDa to600 kDa. A weight average molecular weight of the polymer of 50 kDa orhigher is preferred for processing and mechanical properties.

B. Additives

Certain additives may be incorporated into the implant, preferably inthe absorbable polymer, copolymer or blends thereof that are used tomake the implant. Preferably, these additives are incorporated during acompounding process to produce pellets that can be subsequentlymelt-processed. For example, pellets may be extruded into fiberssuitable for making the implants. In another embodiment, the additivesmay be incorporated using a solution-based process, for example, fibersmay be spun from solutions of the polymer and one or more additives. Ina preferred embodiment, the additives are biocompatible, and even morepreferably the additives are both biocompatible and resorbable.

In one embodiment, the additives may be nucleating agents and/orplasticizers. These additives may be added in sufficient quantity toproduce the desired result. In general, these additives may be added inamounts between 1% and 20% by weight. Nucleating agents may beincorporated to increase the rate of crystallization of the polymer,copolymer or blend. Such agents may be used, for example, to facilitatefabrication of the implant, and to improve the mechanical properties ofthe implant. Preferred nucleating agents include, but are not limitedto, salts of organic acids such as calcium citrate, polymers oroligomers of PHA polymers and copolymers, high melting polymers such asPGA, talc, micronized mica, calcium carbonate, ammonium chloride, andaromatic amino acids such as tyrosine and phenylalanine.

Plasticizers that may be incorporated into the compositions forpreparing the implants include, but are not limited to, di-n-butylmaleate, methyl laureate, dibutyl fumarate, di(2-ethylhexyl) (dioctyl)maleate, paraffin, dodecanol, olive oil, soybean oil, polytetramethyleneglycols, methyl oleate, n-propyl oleate, tetrahydrofurfuryl oleate,epoxidized linseed oil, 2-ethyl hexyl epoxytallate, glycerol triacetate,methyl linoleate, dibutyl fumarate, methyl acetyl ricinoleate, acetyltri(n-butyl) citrate, acetyl triethyl citrate, tri(n-butyl) citrate,triethyl citrate, bis(2-hydroxyethyl) dimerate, butyl ricinoleate,glyceryl tri-(acetyl ricinoleate), methyl ricinoleate, n-butyl acetylrincinoleate, propylene glycol ricinoleate, diethyl succinate,diisobutyl adipate, dimethyl azelate, di(n-hexyl) azelate, tri-butylphosphate, and mixtures thereof. Particularly preferred plasticizers arecitrate esters.

C. Bioactive Agents

The implants can be loaded or coated with bioactive agents. Bioactiveagents may be included in the implants for a variety of reasons. Forexample, bioactive agents may be included in order to improve tissuein-growth into the implant, to improve tissue maturation, to provide forthe delivery of an active agent, to improve wettability of the implant,to prevent infection, and to improve cell attachment. The bioactiveagents may also be incorporated into the structure of the implant.

The implants may contain cellular adhesion factors, including celladhesion polypeptides. As used herein, the term “cell adhesionpolypeptides” refers to compounds having at least two amino acids permolecule that are capable of binding cells via cell surface molecules.The cell adhesion polypeptides include any of the proteins of theextracellular matrix which are known to play a role in cell adhesion,including fibronectin, vitronectin, laminin, elastin, fibrinogen,collagen types I, II, and V, as well as synthetic peptides with similarcell adhesion properties. The cell adhesion polypeptides also includepeptides derived from any of the aforementioned proteins, includingfragments or sequences containing the binding domains.

The implants can incorporate wetting agents designed to improve thewettability of the surfaces of the implant structures to allow fluids tobe easily adsorbed onto the implant surfaces, and to promote cellattachment and or modify the water contact angle of the implant surface.Examples of wetting agents include polymers of ethylene oxide andpropylene oxide, such as polyethylene oxide, polypropylene oxide, orcopolymers of these, such as PLURONICS®. Other suitable wetting agentsinclude surfactants or emulsifiers.

The implants can contain gels, hydrogels or living hydrogel hybrids tofurther improve wetting properties and to promote cellular growththroughout the thickness of the scaffold. Hydrogel hybrids consist ofliving cells encapsulated in a biocompatible hydrogel like gelatin,methacrylated gelatin (GelMa), silk gels, and hyaluronic acid (HA) gels.

The implants can contain active agents designed to stimulate cellin-growth, including growth factors, cellular differentiating factors,cellular recruiting factors, cell receptors, cell-binding factors, cellsignaling molecules, such as cytokines, and molecules to promote cellmigration, cell division, cell proliferation and extracellular matrixdeposition. Such active agents include fibroblast growth factor (FGF),transforming growth factor (TGF), platelet derived growth factor (PDGF),epidermal growth factor (EGF), granulocyte-macrophage colony stimulationfactor (GMCSF), vascular endothelial growth factor (VEGF), insulin-likegrowth factor (IGF), hepatocyte growth factor (HGF), interleukin-1-B(IL-1 B), interleukin-8 (IL-8), and nerve growth factor (NGF), andcombinations thereof.

Other bioactive agents that can be incorporated in the implants includeantimicrobial agents, in particular antibiotics, disinfectants,oncological agents, anti-scarring agents, anti-inflammatory agents,anesthetics, small molecule drugs, anti-angiogenic factors andpro-angiogenic factors, immunomodulatory agents, and blood clottingagents. The bioactive agents may be proteins such as collagen andantibodies, peptides, polysaccharides such as chitosan, alginate,hyaluronic acid and derivatives thereof, nucleic acid molecules, smallmolecular weight compounds such as steroids, inorganic materials such ashydroxyapatite, or complex mixtures such as platelet rich plasma.Suitable antimicrobial agents include: bacitracin, biguanide,trichlosan, gentamicin, minocycline, rifampin, vancomycin,cephalosporins, copper, zinc, silver, and gold. Nucleic acid moleculesmay include DNA, RNA, siRNA, miRNA, antisense or aptamers.

The implants may also contain allograft material and xenograftmaterials, including acellular dermal matrix material and smallintestinal submucosa (SIS).

Additionally, human fat such as autologous fat grafts may be added orinjected across or into the implant scaffolding. Lipoaspirate fattytissue from the patient may be added to the internal surface or externalsurface of the implant. In the case that the implant is porous, thefatty tissue and globules may be held in place within the pores of theimplant.

In another embodiment, the collected fatty tissue is mixed with anatural or synthetic fluidized scaffolding matrix to be added to theimplant to assist in holding the globules of fat in place in theimplant. Examples of natural and synthetic fluidized scaffolding matrixinclude, without limitation, hydrogels, water soluble polymers,polyesters, and hydrophilic polymers, including polyethylene oxide,polyvinyl alcohol, and polymers of fibrin, thrombin, alginate, collagen,chitosan, and silk.

In yet another preferred embodiment, the implants may incorporatesystems for the controlled release of the therapeutic or prophylacticagents.

Components for Preparing Full Contour Breast Implants

A variety of methods can be used to manufacture the implants. Theimplants may comprise the fibers disclosed herein.

Fibers for Making Full Contour Implants

The implants may comprise fibers. The fibers are made from degradablethermoplastic polymers, and even more preferably from degradablethermoplastic polyesters. The fibers are preferably made from thedegradable materials listed above. The fibers maybe monofilament fibers,multifilament fibers, or combinations thereof. Particularly preferredimplants comprise monofilament fibers. The fibers may be unoriented,partially oriented, highly oriented or combinations thereof, but arepreferably oriented. The fibers preferably have elongation to breakvalues of 3% to 100%, more preferably 3% to 50%. The fibers may havediameters ranging from 1 micron to 5 mm, more preferably from 10 micronsto 1 mm, and even more preferably from 50 microns to 500 microns. Thefibers may have weight average molecular weights ranging from 10 kDa to1,200 kDa, but more preferably from 50 kDa to 600 kDa. The fiberspreferably retain at least 50% of their initial strength in vivo for 1-6months, more preferably 2-4 months. The fibers preferably completelydegrade within 5 years of implantation, and more preferably within 2years of implantation. The fibers preferably have initial tensilestrengths ranging from 1 to 1,300 MPa, and more preferably from 50 MPato 1,000 MPa.

In an embodiment, the implants comprise fibers with one or more of thefollowing properties: an elongation to break of 10-100%, and a tensilestrength of 300-1,000 MPa.

In one preferred embodiment, the full contour implants comprise fibersmade from P4HB, and more preferably from P4HB monofilament fiber. TheP4HB monofilament fibers are preferably partially or fully oriented(i.e. partially or fully stretched after extrusion). In one embodiment,P4HB monofilament fiber may be produced according to the followingmethod. Bulk P4HB resin in pellet form is dried to under 300 ppm waterusing a rotary vane vacuum pump system. The dried resin is transferredto an extruder feed hopper with nitrogen purge to keep the pellets dry.The pellets are gravity fed into a chilled feeder section and introducedinto an extruder barrel, with a 1.5 inch (3.8 cm) diameter, and fittedwith an extrusion screw with a 30:1 L/D ratio. The extruder barrelpreferably contains 5 heating zones (or extrusion zones), and ismanufactured by American Kuhne. The heated and softened resin from theextruder is fed into a heated metering pump (melt pump) and from themelt pump the extruded resin is fed into the heated block and an 8-holespinneret assembly. Processing profile ranges from 40° C. to 260° C. fortemperatures, and 400 psi to 2000 psi for pressures. The moltenfilaments are preferably water quenched and optionally conveyed into anorientation line, preferably a three-stage orientation line, andoptionally with inline relaxation, before winding of the monofilamentson spools. This procedure may, for example, be used to produce P4HBmonofilament fibers with one or more of the following properties: anelongation to break from 10-100%, a tensile strength from 50-1,300 MPa,and a tensile modulus from 70-1,000 MPa. The P4HB monofilament fibersmay have average diameters ranging from 20 microns to 1 mm, but are morepreferably 50 microns to 500 microns. In an embodiment, the P4HBmonofilament fibers may have USP (United States Pharmacopeia) sizes 10,9, 8, 7, 6, 5, 4, 3, 2, 1, 0, 2-0, 3-0, 4-0, 5-0, 6-0, 7-0, 8-0, 9-0,10-0, 11-0, and 12-0.

In another embodiment, the full contour implants comprise fibers madefrom P4HB multifilament fiber. Multifilament fibers of P4HB orcopolymers thereof may be spun, for example, as follows: The polymer,copolymer or blend thereof is pelletized, and dried so that the moisturecontent of the polymer, copolymer or blend is less than 300 ppm. Thedried pellets are placed in the feed hopper of an extruder, andprotected from moisture, for example with a dry nitrogen purge. Thepellets are gravity fed into a chilled feeder section, and introducedinto a suitable extruder barrel with an extrusion screw. One suitableextruder barrel has a diameter of 0.75 inches and length of 25.69inches, and is fitted with an extrusion screw with a 30:1 L/D ratio.American Kuhne makes a suitable extruder. In a preferred embodiment, theextruder barrel contains 4 heating zones, and a processing profile isset with temperatures ranging from 40° C. to 300° C. and pressures of200 psi to 3,000 psi. The heated and softened polymer, copolymer orblend is fed into a metering pump, and from the metering pump the resinis fed into the heated block. The spin head is fitted with a spin packcomprising filtering media (screens), and spinnerets containing thedesired number of holes for forming the individual filaments of themultifilament yarn. For example, the spinneret may have 15, 30, 60, 120or more or less holes. The extruded filaments exit the spinneret, andpass through a heated chimney before they are allowed to cool. Spinfinish is preferably applied to the yarn, and the yarn may either becollected on a winder, or oriented in-line. Suitable spin finishesinclude PEG400 and Tween 20. The multifilament fiber may have a tenacitybetween 1 and 12 grams per denier.

P4HB Meshes

The fibers described herein may be processed into meshes, for example,by knitting, weaving, or crocheting. A particularly preferred mesh foruse in preparing the full contour implants is a warp knit mesh.

Implants comprising knitted meshes may be produced using P4HB fibers,preferably P4HB monofilament fibers. Implants comprising P4HBmonofilament oriented or partially oriented fibers have a prolongedstrength retention profile, and can maintain some residual strength foras much as one year. The prolonged strength retention of these P4HBfibers provides an extended period for tissue in-growth into the meshesmade from these fibers, and therefore full contour breast implants madefrom P4HB meshes can prevent early recurrent ptosis while regeneratedtissue is formed around and in the mesh scaffold to support the breast.

A suitable knitted P4HB mesh may be prepared, for example, by thefollowing method. Monofilament fibers from 49 spools are pulled underuniform tension to the surface of a warp beam. A warp is a large widespool onto which individual fibers are wound in parallel to provide asheet of fibers ready for coating with a 10% solution of Tween® 20lubricant. Tween® 20 lubricant is added to the surface of the sheet offiber by means of a ‘kiss’ roller that is spinning and is immersed in abath filled with Tween® 20. The upper surface of the roller is broughtinto contact with the sheet of fiber, and the roller spun at a uniformspeed to provide a consistent application of Tween® 20 finish. Followingthe application of Tween® 20, the sheet of fiber is placed onto a creelposition such that each spooled fiber is aligned and wrapped side byside to the next spooled fiber on a warp beam. Next, warp beams areconverted into a finished mesh fabric by means of interlocking knitloops. Eight warp beams are mounted in parallel onto a tricot machinelet-offs and fed into the knitting elements at a constant ratedetermined by the ‘runner length’. Each individual monofilament fiberfrom each beam is fed through a series of dynamic tension elements downinto the knitting ‘guides’. Each fiber is passed through a single guide,which is fixed to a guide bar. The guide bar directs the fibers aroundthe needles forming the mesh structure. The mesh fabric is then pulledoff the needles by the take down rollers at a constant rate of speed.The mesh fabric is then taken up and wound onto a roll. The P4HBmonofilament mesh produced according to this method may be scoredultrasonically with water, optionally heat set in hot water, andoptionally washed with a 70% aqueous ethanol solution.

Methods for Preparing Full Contour Breast Implants

A variety of methods can be used to manufacture the full contourimplants.

Shapes

In an embodiment, the absorbable implants are designed so that whenmanufactured, they are three-dimensional. Their shape allows the breastto be contoured, and the volumes of the upper and lower pole to becontrolled without any buckling or bunching of the implant or tissuestructures. The implants have volumetric dimensions that producespecific breast shapes when implanted. Specifically, the implant'svolumetric dimensions sculpt the breast so that the ratio of the upperpole volume (UPV) to the lower pole volume (LPV) is pre-defined by theimplant. Thus, the volumetric dimensions of the implant produce aparticular breast appearance wherein the ratio of the UPV to the LPVfalls within a relatively narrow range.

For example, with reference to FIG. 3, an aesthetically pleasing breast10 is shown having a three-quarter profile, where 28% of the volume ofthe breast is in the upper pole 20 of the breast, 72% of the volume ofthe breast is in the lower pole 30 of the breast, the NPL 52corresponding to the NAC on the breast is angulated slightly skyward,and the ratio of the height of the upper pole of the breast to the lowerpole of the breast measured along the natural sloping angle of the chestwall reference (CWR) line 12 is 70:40.

However, the invention is not so limited. In other embodiments, theimplants have a three-dimensional shape that results in a breast havingone or more of the following properties: (i) an upper pole volume (UPV)of 25-35% of the total breast volume, (ii) lower pole volume (LPV) of65-75% of the total breast volume, and a nipple angled on the breastpointing slightly skyward at 12-27 degrees above the nipple meridianreference (NMR) line, more preferably 18-22 degrees above the NMR line.

In addition to sculpting the breast with specific volumetric ratios oftissue in the upper and lower poles, the dimensions and shape of theimplant can also be chosen to provide very desirable shapes of the lowerpole, upper pole, and extent of projection of the breast from the chestwall. In particular, the implants are designed so that (a) the lowerpole has a very attractive lower pole curvature, specifically anattractive convex shape, (b) the upper pole has a straight (as shown inFIG. 4A) or slightly concave curvature (as shown in FIG. 4B), and (c)the distance the breast projects from the breast wall is defined.

In a further preferred embodiment, the implant's shape is designed sothat the angulation of the patient's nipple can be controlled, and canbe placed at a specific position on the reconstructed breast.

With reference to FIG. 5, the implant is configured to control theposition of the patent's nipple so that it is angulated slightlyskyward, preferably the nipple is positioned at an angle of 10-30degrees above the nipple meridian reference (NMR) line, and in someembodiments 12-27 or 13-27 degrees above the NMR line, and morepreferably 18-22 degrees above the NMR line. In embodiments, the implantsupports or remodels the breast where the nipple is positioned at anangle greater than 10 and less than 20 degrees above the NMR line.

With reference to FIGS. 6A-6D, front, lateral, top and isometric viewsof a full contour implant 100 are shown respectively. The implant 100includes a NAC feature 110, guiding flexible pillars 120, and attachmenttabs 130 on the outer edge of the implant.

In embodiments, the implants have an opening 110, preferably a circularopening or “NAC feature”, through which the nipple areola structure canbe placed. The opening 110 can be smooth and may also be reinforced 112as described further herein.

The implant 100 shows pillars 120 which, as described further herein,reinforce the shape of the implant, and direct the tissue to thepredetermined shapes. The pillars may be additional fused materialincluding, e.g., mesh, foam or other material as described herein.

Tabs 130 are shown at the 12-, 3-, 6-, and 9-O-clock positions. Asdescribed further herein, tabs 130 provide additional material for thephysician to suture or attached the implant in place.

The implant 100 is also shown having a superior end 116 at least aslarge as the inferior end 114. With reference to FIG. 6B, the UPcurvature is straight or a bit concave and the LP curvature is clearlyconvex

It will therefore be apparent that the implants of the invention can beused to produce a very attractive reconstructed breast by havingspecific shapes that (i) define the ratio of the UPV to the LPV; (ii)define the curvatures of the upper and lower poles; (iii) define theextent of projection of the breast from the chest wall; and (iv) definethe angulation of the nipple on the breast.

In order to produce a very attractive reconstructed breast with thespecific shapes described herein, the dimensions of the implant aredesigned to allow for the volume occupied by the skin flap that coversthe implant after implantation in the breast. In other words, a breastwith a UPV of 25-35% of the total breast volume, and a LPV of 65-75%, isformed as a result of the volume of the implant plus the volume of theskin flap. Typically, a skin flap used by a surgeon to cover the implantwill be 0.5-4 cm thick, more preferably 1-3 cm thick, and is generallywider closer to the chest wall than to the NAC. Accordingly, thedimensions of the implant used in the procedure of the invention are notthe same as the dimensions of the final reconstructed breast. Theimplants disclosed herein preferably have an upper pole volume of20-400%, more preferably 23-35%, and even more preferably 25-31%, and alower pole volume of 60-80%, more preferably 65-75%, and even morepreferably 69-75%. When overlaid with the patient's skin flap, a breastwith a UPV of 25-35% and LPV of 65-75% is produced.

In embodiments, the thickness of the implant varies. In embodiments, thethickness from the perimeter to the center or NAC opening decreases. Inother embodiments, the thickness from the perimeter to the center or NACopening increases. As described further herein, the thickness of theimplant may be adjusted by adding a layer such as foam, collagen, orfusing additional material to select locations or making redundantlayers.

An example of an implant 400 including a redundant layer or second layer410 is shown in FIGS. 14-15. The second layer may be a biocompatiblecoating (e.g., collagen type I). The coating 410 is shown covering afirst layer or mesh 420 in the area corresponding to the NAC, serving toreduce friction on the skin when the device is implanted underneath theskin. However, the shape and area of the second layer 410 may vary. Itmay extend and coat the entire first layer 420, or may be smaller andlocated to cover different areas including, for example, triangular,square or rectangular-shaped discreet regions, etc.

Within the scope described herein, it should be understood that theshapes and dimensions of the implants can vary over certain specificranges. The implants can be prepared in sizes large enough to allow fortheir use in mastopexy and breast reconstruction, with or withoutpermanent implants. The implants are wide enough to span the width of abreast.

In an embodiment, there are a plurality of sizes (e.g., an implant kit).In an embodiment, there are four sizes and shapes of implant namely,small, medium, large, and x-large. The dimensions of these implants areshown in Table 1, below, wherein IMF-UP is the longitudinal distancebetween the implant's lowest point, IMFR, (which will be located nearestthe IMF of the breast after implantation) and highest point, UPUR,(which will be located nearest the intersection between the breast andchest wall in the upper pole after implantation), MD-LT is the implantwidth measured from the medial to lateral side of the implant, CHST-NACis the protrusion distance of the implant from the opening in theimplant for the NAC to the intersection of the IMF-UP and MD-LT lines,NAC-ID is the size of the inner diameter of the cutout in the implantthat is left open for the patient's NAC, and NAC-OD is the outsidediameter of the NAC feature in the implant as shown in FIG. 7A. Thedistance between the NAC-ID and NAC-OD determines the width of the NACfeature, and the NAC feature's location determines the angulation of thenipple on the breast. The lower pole radius (LP Radius) shown in Table1, and in FIG. 7A, defines the convex shape of the implant that will bepositioned over the lower pole of the breast. The LP Radius is measuredfrom the point of intersection of the IMF-UP and MD-LT lines, to theconvex surface of the implant in the region where the implant isdesigned to cover the lower pole.

TABLE 1 Dimensions for implants shown in FIG. 7 (excluding tabs) IMF-UPMD-LT CHST-NAC NAC-ID NAC-OD LP Radius Size (cm) (cm) (cm) (cm) (cm)(cm) Small 12-14 10.8-12.5  5-6.4 2.5-2.9 3-3.4 4.2-4.6 Medium   14-16.212.5-14.5 6.4-7.9 2.9-3.5 3.4-4     5-5.4 Large 16.2-18.5 14.5-16.77.9-9.6 3.5-4.3 4-4.8 5.8-6.4 X-Large 18.5-20.8 16.7-19.2  9.6-11.94.3-5.3 4.8-5.8  6.8-7.6

Based on the table, the inventors discovered that implants may have anfMF-UP dimension of 12-20.8 cm, a MD-LT dimension of 10.8-19.2 cm, aCHST-NAC dimension of 5-11.9 cm, a NAC-ID dimension of 2.5-5.3 cm, aNAC-OD dimension of 3-5.8 cm, and a LP radius of 4.2-7.6 cm.

The implants may also be defined by the ratio of the LP Radius, to theUP Height shown in FIG. 7A. The UP Height is the distance from theimplant's highest point to the intersection of the IMF-UP and MD-LTlines as shown in FIG. 7A. The IMF-UP length is equal to the sum of thelengths of “LP Radius” and “UP Height”. In an embodiment, the implant'sratio of UP Height:LP Radius should be 2-2.5:1, and more preferably2.2:1.

The curvature of the implant that forms the upper pole of the breast mayalso vary. It may be slightly concave or straight, and is defined by thevolumetric ratio of the implant's upper pole to lower pole. This ratio(UPV:LPV of the implant) ranges from 20:80 to 40:60, more preferably25:75 to 35:65, and even more preferably 28:72. Isometric views of theimplant's upper pole volume (UPV) and lower pole volume (LPV) are shownin FIGS. 7B-7C respectively.

In another embodiment, the implant's dimensions are further defined bythe protrusion of the implant from the chest wall shown as depth(namely, the distance CHST-NAC in FIG. 7A) and ranges from 5 to 12 cm,or falls within one of the subgroups 4-6; 7-9; and 10-12 cm.

In another embodiment, the implant's dimensions are further defined by(i) the protrusion of the implant from the chest wall shown as CHST-NACin FIG. 7A, and (ii) the distance from the bottom of the implant to thetop of the implant shown as IMF-UP in FIG. 7A.

The implant shapes may have one or more of the following properties(with reference to FIG. 7A): (i) a shape that is filled with 25-35% ofthe UPV of the breast; (ii) a shape that is filled with 65-75% of theLPV of the breast; (iii) a shape that is filled with a breast volumeratio of UPV:LPV of 28:72; (iv) a cutout positioned in the implantlocated so that the nipple areola complex can only be positioned at 12(or 13) to 27 degrees above the NMR line, and more preferably at 18-22degrees; (v) a convex curvature of the lower pole (LP) radius of theimplant; (vi) a straight or slightly concave curvature of the upper poleof the implant between the opening for the NAC and upper pole upperreference point (UPUR) as shown in FIG. 7A; (vii) a ratio of UPHeight:LP Radius of 2-2.5:1, and more preferably 2.2:1; (viii) a IMF-UPdimension of 12-20.8 cm, or 10-21 cm (ix) a MD-LT dimension of 10.8-19.2cm, or 10-20 cm (x) a CHST-NAC dimension of 5-11.9 cm, or 5-12 cm (xi) aNAC-ID dimension of 2.5-5.3 cm, or 2-6 cm (xii) a NAC-OD dimension of3-5.8 cm, 2.5-6 cm and (xiii) a LP radius of 4.2-7.6 cm 4-8 cm.

FIGS. 7D-7E show isometric and left profile views, respectively, of theimplant after it has been implanted in the breast and overlaid with thepatient's skin flap resulting in a reconstructed breast with a UPV of25-35% and LPV of 65-75%.

The implants disclosed herein may optionally be reinforced, for example,by flexible pillars 120 as shown in FIGS. 6A-6D. The flexible pillarsare preferably located on the implant around the NAC, from the NAC tothe outer perimeter of the implant, and around the outer perimeter ofthe implant.

Properties of the Implants

The absorbable implants have been designed to support the mechanicalforces acting on the breast during normal activities at the time ofimplantation, and to allow a steady transition of mechanical forces toregenerated host tissues that can also support those same mechanicalforces once the implant has degraded. The implants disclosed hereinpreferably have burst strengths between 0.6 and 90 N/cm², morepreferably between 1.2 and 30 N/cm². Preferably, the implant's burststrength 3 months after implantation is at least 40% of its initialburst strength.

The implants are preferably porous, and can be replaced in vivo by hosttissue growing into and around the implant that is strong enough tosupport the breast. The diameters of the implant's pores are preferablylarger than 25 μm, more preferably larger than 75 μm, and even morepreferably larger than 250 μm in order to facilitate tissue in-growth,but smaller than 10 mm, more preferably smaller than 5 mm, and even morepreferably smaller than 2 mm. Non-limiting examples of porous constructsthat can be used to make the implant include mesh construct, fabricconstruct, woven construct, non-woven construct, knitted construct,braided construct, porous film construct including laminated andperforated film construct, nanospun construct, electrospun construct, ormelt-blown construct, and combinations thereof, as well as thermoformsof these constructs. Preferably, these constructs are made from P4HB,and even more preferably from oriented, partially oriented, orunoriented P4HB monofilament textiles.

The implant can be designed so that it stretches equally in eachdirection. The implant may also be designed so that it may stretch morein some directions than in other directions. The ability of the implantto stretch can allow the surgeon to place tension on the breast duringimplantation. However, in order to maintain support for the breastfollowing surgery, it is important that after the implant is implanted,the implant, the regenerated host tissue, and any transitionalstructures, cannot stretch significantly. In an embodiment, the implantcannot stretch more than 30% of its original length in any direction. Inan even more preferred embodiment, the implants cannot stretch more than20% of their original length in any direction and comprise fibers ofpoly-4-hydroxybutryate or copolymer thereof with elongation to breakvalues of 25-95%, more preferably 25-55%.

In one embodiment, the implants can be temporarily deformed and resumetheir original three-dimensional preformed shapes after implantationinto a suitably dissected tissue plane.

In a particularly preferred embodiment, the full contour implants aresutured in place. Without intending to being bound to theory, the loadexerted by the breast is spread out over the implant, the entire forceof the breast tissue is shared among the points of attachment of theimplant to the body. An advantage of the absorbable implants disclosedherein is that they possess a high suture pullout strength that allows aheavy breast to be supported with a limited number of anchoring sites.In a preferred embodiment, an implant is anchored to the chest wall atfour or more places, preferably 4-12 places, in order to support thebreast. This strategy distributes the load over multiple attachmentpoints. In a particularly preferred embodiment, the implant has tabswith high suture pullout strengths, preferably 2-20 tabs, morepreferably 4-12 tabs, that are located around the edges of the implantto allow suturing of the implant to the tissue surrounding the breastglandular tissue. The dimensions of the tabs are preferably from 0.5cm×0.5 cm to 5 cm×4 cm, preferably 2 cm×2.5 cm. The implant and any tabsmust have sufficient strength retention in vivo to resist mechanicalloads while tissue in-growth occurs. In a particularly preferredembodiment, the suture pullout strength of the absorbable implant, andany tabs attached thereto, is greater than 10 N, and more preferablygreater than 20 N. In one embodiment, these suture pullout strengths canbe obtained if the implants, and any tabs attached thereto, compriseoriented P4HB monofilament fibers, more preferably knitted oriented P4HBmonofilament fibers, and even more preferably oriented P4HB monofilamentfibers that have been formed into a textile structure.

In an embodiment, the three-dimensional implant has properties thatallow it to be delivered through a small incision. The implant may, forexample, be designed so that it can be rolled or folded to allowdelivery through a small incision. This minimally invasive approach canreduce patient morbidity, scarring and the chance of infection. In aneven more preferred embodiment, the implant has a three-dimensionalshape and shape memory properties that allow it to assume its originalthree-dimensional shape unaided after it has been delivered through anincision and into an appropriately sized dissected tissue plane. Forexample, the implant may be temporarily deformed by rolling it up into asmall diameter cylindrical shape, delivered using an inserter, and thenallowed to resume its original three-dimensional shape unaided in vivo.Flexible pillars, such as those shown in FIG. 6, may be incorporatedinto the implant in order to facilitate implantation, and to allow theimplant to regain shape more easily after implantation. The pillarspreferably have diameters or widths ranging from 0.5 to 3 mm, and arepreferably made from unoriented, partially or fully oriented P4HBpolymer or copolymer thereof.

Construction of the Implants

A variety of methods can be used to manufacture the implants, and theirscaffold structures.

In a particularly preferred embodiment, the implants are prepared bymolding a porous construct into a three-dimensional shape using a moldthat has the shape of a breast and specific volumetric ratios in theupper and lower parts of the mold. The volumetric ratios of the mold areselected to produce an implant that will redistribute the tissues of thebreast so that the volume occupied by the upper pole of the breast is25-35% of the total volume, and the volume occupied by the lower pole ofthe breast is 65-75% of the total volume. More preferably the implantredistributes the breast volume so the upper pole to lower polevolumetric ratio is 28:72.

An example of a mold 200 with these volumetric ratios is shown in FIG.8A. In addition to having specific volumetric ratios, the mold is shapedto have a convex curvature in the lower pole and a straight to slightlyconcave curvature in the upper pole. For illustration purposes, theposition of a nipple is shown on the mold. The mold is designed toproduce an implant where the location of the nipple, after implantationof the implant, will be between 12 (or 13) and 27 degrees above thenipple meridian reference (NMR) line of the breast, more preferablybetween 18 and 22 degrees above the NMR line. After molding, the areaaround the nipple of the implant is cutout so the patient's NAC mayprotrude through the opening upon implantation.

The mold shown in FIG. 8A has an outer flat edge 210 with holes 220 thatallow connection to a pressure ring 230 (also shown in FIG. 8A). Aporous construct 240, such as a two-dimensional mesh, preferably amonofilament mesh, may be inserted in the mold as shown in thecross-sectional diagram in FIG. 8B, and held under tension by an O-ringpresent in a groove in the pressure ring. When the pressure ring isclamped to the breast shaped plate, the O-ring presses on the porousconstruct to keep it from moving, and prevents the porous construct fromshrinking during molding. To impart the desired implant shape to theporous construct, the non-porous construct 240 held under tension in themold assembly may be thermoformed, and then removed from the mold. In apreferred embodiment, an oriented P4HB monofilament mesh is thermoformedby placing the assembly of the mold and mesh in hot water, and thenquenching the mesh by placing the assembly of the mold and mesh in coldwater. The oriented P4HB monofilament mesh preferably has an arealdensity of 5 to 800 g/m². In a particularly preferred embodiment, theassembly containing the P4HB monofilament mesh is placed in hot waterwhere the temperature is 55-63° C., more preferably 56-58° C., for 3-10minutes, more preferably 3-5 minutes, and then quenched in cold waterwhere the temperature is 2-12° C., more preferably 6-10° C., for 2-15minutes, more preferably 5-10 minutes.

FIG. 9 shows a porous construct 240 on a mold that has been thermoformedusing the mold shown in FIG. 8A. In this example, the porous constructis a P4HB mesh made from oriented P4HB monofilament fibers. FIG. 9 showsthe molded P4HB mesh in the mold with excess material 242 around theedge of the mold. This excess material may be removed by trimming, forexample, to form the implant 250 shown in FIG. 10.

FIG. 11 shows a hole 260 cut in the implant of FIG. 9 to accommodate thepatient's NAC.

With reference to FIG. 12, a mesh 280 is shown having tabs 270 aroundthe perimeter 272 of the mesh. The tabs may be formed by trimming aroundthe perimeter of the mesh described above. The number of tabs may vary.In embodiments, there are 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20 tabs or more, but preferably 4-12. FIG. 12 showsan implant 280 with 12 tabs.

The porous construct molded as described above may optionally furthercomprise guiding flexible pillars. A diagram of an implant comprisingguiding flexible pillars is shown in FIG. 6A. In this example, theguiding flexible pillars run in straight direct lines between the NACand the outer edge of the implant over the outer surface of the implant.FIG. 6A shows four guiding flexible pillars connecting the NAC to theouter edges of the implant. However, the number of guiding pillars mayvary and may be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more, butpreferably 4-12. The flexible guiding pillars may be incorporated intothe implants by any suitable method, including fusion, molding, knittingor printing either before or after molding. In one embodiment, theflexible guiding pillars are incorporated by fusing absorbable polymericfibers to the implant. Preferably, unoriented fiber extrudate is fusedto the implants. In a particularly preferred embodiment, unoriented P4HBfiber extrudate may be fused to the implant, preferably an implant alsomade from P4HB, particularly a P4HB monofilament mesh. In anotherembodiment, flexible guiding pillars may be printed directly onto theporous construct before molding, or after molding. Preferably anabsorbable thermoplastic, such as P4HB, is printed.

In another embodiment, the cutout or aperture 110 in the implant forreceiving the patient's NAC may be further modified as indicated by the“NAC Feature” shown in FIG. 6A. This can be particularly desirable ifthe edges of the cutout are sharp or rough. For example, cutting out ahole from a monofilament mesh to receive the patient's NAC will resultin a non-smooth edge that could irritate surrounding tissues uponimplantation. A smoother opening for the NAC can be made, for example,by fusing a fiber 112 around the circumference of the cutout so thesharp ends of the cutout are smoothly sealed, or printing an absorbablethermoplastic on the sharp ends. In a preferred embodiment, a P4HB fiberextrudate is fused around the circumference of the cutout to form a “NACFeature”. Even more preferably, the P4HB fiber extrudate is fused aroundthe circumference of an NAC cutout in an implant made from P4HBmonofilament mesh.

Other porous constructs, besides monofilament meshes, may be molded toform the implants. For example, the porous constructs may comprisemultifilament fibers, or combinations of monofilament and multifilamentfibers. These porous constructs may be woven or knitted. The porousconstructs may be produced by either warp or weft knitting processes,however, a warp knit is preferred in order to minimize the stretching ofthe implant. A P4HB warp knitted mesh made from oriented P4HBmonofilament fiber is particularly preferred.

The porous construct for molding into the implants may alternativelycomprise perforated films (oriented or un-oriented), non-wovens,laminates, electrospun fabric, solvent and melt spun fabric, foam,thermally bonded fibers, wet or solution spun fibers, dry spun fibers,thermoforms, or other porous materials. The porous construct may also beprepared by a process that uses particulate leaching, preferably whereinthe leachable particle materials have a diameter of at least 50 μm, morepreferably at least 75 μm, but less than 5 or 10 mm. Alternatively, theporous constructs may be prepared by phase separation. The porousconstruct may be a combination of two or more materials.

The processes described herein to produce the implants can also be usedin combination. For example, a woven construct could be combined with anon-woven construct, and molded to form an implant. Or, an implant couldbe prepared by printing on a mesh.

In still another embodiment, the implants may be prepared by methodsthat include 3D printing (also known as additive manufacturing). Thismethod is particularly useful in the manufacture of specific shapessince the desired shape can be made directly without the need forfurther cutting or trimming. In a preferred embodiment, the implant ismade by 3D printing with P4HB, more preferably 3D printing incombination with a mold.

In another embodiment, the implants comprise retainers, such as barbs ortacks, so that the implant can be anchored to the chest wall in certainplaces without the use of sutures. For example, the three-dimensionalimplants may contain retainers in their outlying borders to anchor theimplants.

The implants can be trimmed or cut with scissors, blades, other sharpcutting instruments, or thermal knives in order to provide the desiredimplant shapes. The implants can also be cut into the desired shapesusing laser-cutting techniques. This can be particularly advantageous inshaping fiber-based implants because the technique is versatile, andimportantly can provide shaped products with sealed edges that do notshed cut loops or debris produced in the cutting process.

Methods for Implanting the Full Contour Breast Implants

The implants described herein are most suited for use in breast surgery,and more particularly for mastopexy or mastopexy augmentationprocedures. However, the implants may also be used in other proceduressuch as revision procedures following the removal of a breast implant,and breast reconstruction procedures following mastectomy, particularlywhere it is desirable to retain the position of a silicone or salinebreast implant.

In an embodiment, a method of implantation of the implants comprises atleast the steps of: (i) making at least one incision to gain access tothe breast tissue of the patient, (ii) separating the skin andsubcutaneous fascia from the breast mound of the breast, (iii)positioning the implant on the breast mound of the breast so that theNAC protrudes through the opening for the NAC in the implant (and theimplant is oriented so that the convex curvature of the implant contactsthe lower pole of the breast tissue, the straight or slightly concavecurvature of the implant contacts the upper pole of the breast tissue,and the nipple is angulated in a slightly skyward direction), (iv)securing the implant to the tissue surrounding the breast mound of thebreast, and (v) closing the incisions in the breast.

In one embodiment, the breast may be prepared for receiving the implantby making a Wise-type or inverted T-type incision. In this procedure,incisions are made around the areolar complex, vertically in the lowerpole of the breast from the IMF to the areolar complex, and along theinframammary fold to form an inverted T-pattern. In a variation of thisprocedure, two vertical incisions may be made in the lower pole of thebreast to increase access to the underlying breast tissue. Thisprocedure may also be employed when it is desirable to remove excessskin from the lower breast. The skin between the two incisions may beremoved, and at the end of the procedure the two incisions may bejoined, for example, by suturing.

In an alternative surgical approach, the breast can be prepared for theimplant using a less invasive procedure. This is accomplished by makingan incision around the areolar (a peri-areolar incision), and thenexposing the breast tissue by pulling the skin away from the areolar.The advantage of this approach is that scarring of the skin isminimized, and the areolar structure is not damaged.

The breast may also be prepared to receive the implant using a lollipopprocedure wherein an incision is made around the areolar (a peri-areolarincision), and a vertical incision is made in the lower pole from theareolar complex to the inframammary fold.

Once the T-type, peri-areolar or lollipop incisions have been made, thesurgeon may prepare the breast to receive the implant by separating theskin and subcutaneous fascia from the breast mound of the breast.Dissection is performed in the subcutaneous plane around the breastsuperior to the subclavicular, sterno-clavicular and anterior axillaryregions and medially to the parasternal region as well as laterally tothe anterior axillary line in a manner that provides an adequate flapthickness. After dissection is complete, the surgeon selects thecorrectly sized implant. The surgeon can optionally use transparentsterile sizing guides (e.g. shapes molded in the same size as theimplants with cutouts for the NAC) to assist with this process byinserting these guides into the exposed breast between the breast moundand the skin until the desired size is identified. If a guide is toosmall, it will not be possible to locate all the breast tissueunderneath it, and therefore an implant of the same size would be toosmall. If the guide is too large, the underlying breast tissue will befree to move about and will not be proportioned in the desiredvolumetric ratios for the upper and lower poles. Once the guide with theoptimum dimensions is identified, the correctly sized implant can beselected and inserted into the breast. The implant is inserted into thebreast under the skin and positioned to cover the exposed breast moundby pulling the skin away to the extent necessary. The surgeon maymanipulate the implant by hand to make sure it is correctly positioned,and also to make sure there are no wrinkles in the implant. Optionally,the surgeon may also temporarily insert a transparent molded guide ontop of the implant to smooth the placement of the implant on the breasttissue, and if desired, to hold the implant in place while it isfixated. Once the implant has been located in the desired position, itmay be secured in place, for example, by suturing the implant to thetissue surrounding the breast mound. The implant is preferably suturedto the fascia surrounding the pectoral muscle underlying the breastmound.

In a particularly desired embodiment, the implant comprises one or moretabs as shown in FIGS. 6A and 12 that can be sutured to the tissuesurrounding the breast mound. The implant may have 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more tabs that canbe used to secure the implant in place, but preferably 4-12 tabs.

Once the implant has been fixated, the breast can be closed by suturingthe incision lines closed. In embodiments, an implant is fixated in bothbreasts. After the procedure is completed in one or both breasts, andthe patient is standing upright, the total breast volume will bedistributed so that the tissue volume in the upper pole of each breastis 25-35%, and the tissue volume in the lower pole of each breast is65-75%. The patient's lower poles will have a convex shape, and theupper poles will have a straight or slightly concave shape. Furthermore,the patient's nipples will be pointing slightly skyward angulatedbetween 12 (or 13) and 27% above the nipple median reference (NMR) line.Inventors have discovered that, amongst other things, controlling thedepth of the implant (namely, the distance CHST-NAC or projection line)serves to support the breast in a desired shape.

In another embodiment, the procedures described above can be performedwith breast implant augmentation. For example, a permanent breastimplant may be implanted to increase breast volume. The permanent breastimplant may, for example, be a silicone or saline implant.

In a further embodiment, the procedures described above can be performedwith removal of breast tissue, resection and redistribution of breasttissue.

The present invention will be further understood by reference to thefollowing non-limiting examples.

Example 1: Preparation of a Full Contour Absorbable Breast Implant

A full contour breast implant was prepared from a P4HB monofilament meshwith a MARLEX® knit pattern that was derived from a size 5-0 orientedP4HB monofilament fiber with an elongation to break of 25%, and a weightaverage molecular weight of 350 kDa. The mesh was scoured after knittingto remove textile processing aids, and then cut into oval pieces thatwere 50% larger than the base of the 3D breast-shaped mold show in FIG.8A. Prior to molding the mesh into the three-dimensional shape, P4HBunoriented extrudate with a diameter of 0.8-1.2 mm, was fused to themesh to form guiding flexible pillars and a NAC feature so that aftermolding these features would have the positions shown in FIG. 6. TheP4HB unoriented extrudate was fused to the mesh using two flat moldsthat applied tension to the mesh. The molds were heated to 57° C. for 5minutes, and then the assembly of the mold and mesh was quenched at 9°C. for 10 mins before dismantling the mold.

To impart a precise three-dimensional shape to the implant with specificvolumetric ratios of the lower and upper poles, the three-dimensionalmold shown in FIG. 8A was used. The mold shown in FIG. 8A is shaped suchthat the breast volume will be distributed in the patient so that theupper pole volume (UPV) is between 25-35%, and the lower pole volume(LPV) is between 65-75%, of the total breast volume, and wherein themold will produce a three-dimensional shape that angulates the patient'snipple between 12 (or 13) and 27% above the nipple median reference(NMVR) line. The P4HB mesh with unoriented extrudate attached asdescribed above was placed over the mold shown in FIG. 8B, and fastenedunder tension using the pressure ring shown in FIG. 8B. It is importantto apply tension on the mesh to prevent shrinkage of the mesh duringmolding. Tension is applied on the mesh by contact with an inner O-ringthat sits in a groove in the pressure ring 230 as indicated in FIG. 8B.The pressure ring can be fastened to the mold using clamps. Once theassembly of the mold was completed, the assembly was placed in hot waterheated to 57° C. for 5 minutes, and then quenched in a cold-water bathwith a temperature of 9° C. for 10 minutes to form the three-dimensionalimplant shape. After quenching, the assembly with excess mesh visiblearound the outside edge of the mold was removed from the cold-waterbath. To complete the preparation of the implant, the clamps arereleased, the mold disassembled, excess mesh trimmed from the implant,and the NAC opening made using a round die cutter and press. Theresulting implant 300 is shown in FIG. 13 with the outer edge 310covered by the pressure ring 320. Optionally, the mesh may be trimmed sothat the implant comprises one or more attachment tabs as shown in FIG.6. These tabs can be used by the surgeon during implantation to orientand fixate the implant at specific locations.

Similar implants may be prepared using (i) P4HB monofilament withelongation to break values of 25-95%, preferably 55-95%, (ii) P4HBpolymer weight average molecular weights of 250-600 kDa, (iii) P4HBunoriented extrudate with diameters ranging from 0.5-2 mm, (iv) moldingof the P4HB mesh in hot water with a temperature of 55-63° C. for 3-10minutes, and (v) quenching of the P4HB mesh in cold water with atemperature of 2-12° C. for 2-15 minutes.

Modifications and variations of the methods and compositions will beapparent from the foregoing detailed description and are intended tocome within the scope of the appended claims.

1-18. (canceled)
 19. A method of manufacturing the implant comprisingthe steps of: (i) preparing a three-dimensional mold in the shape of animplant, (ii) molding a porous two-dimensional construct into athree-dimensional shape using the three-dimensional mold, (iii) removingthe molded shape from the mold, and (iv) cutting an aperture in themolded three-dimensional shape in a position to angulate the patient'sNAC slightly skyward so that the angle between the nipple projectionline and the nipple meridian reference line is 1-27 degrees afterimplantation.
 20. The method of claim 19 further comprising (v) trimmingan edge of the implant to add one or more tabs to the implant.
 21. Themethod of claim 19 further comprising molding a first flexible pillararound the circumference of the aperture to form a NAC feature.
 22. Themethod of claim 19, wherein the porous two-dimensional construct is amonofilament mesh.
 23. The method of claim 19, further comprisingmolding a plurality of reinforcing pillars radially extending from theaperture to an outer edge of the implant. 24-31. (canceled)
 32. Themethod of claim 19, wherein a volume occupied by an upper pole of thepatient's breast is 25-35% of a total volume of the moldedthree-dimensional shape.
 33. The method of claim 19, wherein the implantis shaped to redistribute the patient's breast volume so that an upperpole to lower pole volumetric ratio is 28:72.
 34. The method of claim19, wherein the mold comprises an outer flat edge with a plurality ofholes.
 35. The method of claim 19, further comprising connecting themold to a pressure ring.
 36. The method of claim 19, wherein the step ofmolding the porous two-dimensional construct comprises inserting theporous two-dimensional construct in the mold and holding the poroustwo-dimensional construct under tension.
 37. The method of claim 36,wherein the porous two-dimensional construct is held under tension by anO-ring.
 38. The method of claim 37, wherein the O-ring is present in agroove in a pressure ring.
 39. The method of claim 19, furthercomprising placing the mold in hot water during step (ii).
 40. Themethod of claim 19, further comprising quenching the mold during step(ii).
 41. The method of claim 19, further comprising fusing unorientedfiber extrudate to the implant.
 42. The method of claim 19, furthercomprising fusing a fiber around a circumference of the aperture. 43.The method of claim 42, wherein the fiber comprises apoly-4-hydroxybutyrate (P4HB) fiber extrudate.
 44. The method of claim19, further comprising printing an absorbable thermoplastic on at leasta portion of a circumference of the aperture.
 45. The method of claim19, wherein the implant is absorbable.